UK Department of Health
  • London, United Kingdom
Recent publications
An 11‐year‐old presented with bilateral renal cell carcinoma (RCC) with FH‐deficient RCC confirmed by immunohistochemistry. WGS confirmed no coding variants but identified a rare intronic variant in FH (c.1391‐269A>G). We illustrate how combined pathological and genomic investigations enabled a precise diagnosis of the underlying cause of an ultra‐rare clinical presentation. image
BACKGROUND Dilated cardiomyopathy (DCM) appears to be diagnosed twice as often in male than in female patients. This could be attributed to underdiagnosis in female patients or sex differences in susceptibility. Up to 30% of cases have an autosomal dominant monogenic cause, where equal sex prevalence would be expected. The aim of this systematic review, meta-analysis, and population study was to assess the sex ratio in patients with DCM, stratified by genetic status, and evaluate whether this is influenced by diagnostic bias. METHODS A literature search identified DCM patient cohorts with discernible sex ratios. Exclusion criteria were studies with a small (n<100), pediatric, or peripartum population. Meta-analysis and metaregression compared the proportion of female participants for an overall DCM cohort and the following subtypes: all genetic DCM, individual selected DCM genes ( TTN and LMNA ), and gene-elusive DCM. Population DCM sex ratios generated from diagnostic codes were also compared with those from sex-specific means using the UK Biobank imaging cohort; this established International Classification of Diseases, 10th revision–coded, novel imaging–first, and genotype-first–determined sex ratios. RESULTS A total of 99 studies, with 37 525 participants, were included. The overall DCM cohort had a 0.30 female proportion (95% CI, 0.28–0.32), corresponding to a male:female ratio (M:F) of 2.38:1. This was similar to patients with an identified DCM variant (0.31 [95% CI, 0.26–0.36]; M:F 2.22:1; P =0.56). There was also no significant difference when compared with patients with gene-elusive DCM (0.30 [95% CI, 0.24–0.37]; M:F 2.29:1; P =0.81). Furthermore, the ratio within autosomal dominant gene variants was not significantly different for TTN (0.28 [95% CI, 0.22–0.36]; M:F 2.51:1; P =0.82) or LMNA (0.35 [95% CI, 0.27–0.44]; M:F 1.84:1; P =0.41). Overall, the sex ratio for DCM in people with disease attributed to autosomal dominant gene variants was similar to the all-cause group (0.34 [95% CI, 0.28–0.40]; M:F 1.98:1; P =0.19). In the UK Biobank (n=47 549), DCM defined by International Classification of Diseases, 10th revision, coding had 4.5:1 M:F. However, implementing sex-specific imaging-first and genotype-first diagnostic approaches changed this to 1.7:1 and 2.3:1, respectively. CONCLUSIONS This study demonstrates that DCM is twice as prevalent in male patients. This was partially mitigated by implementing sex-specific DCM diagnostic criteria. The persistent male excess in genotype-positive patients with an equally prevalent genetic risk suggests additional genetic or environmental drivers for sex-biased penetrance. REGISTRATION URL: https://www.crd.york.ac.uk/prospero ; Unique identifier: CRD42023451944.
Two recent reviews in the International Journal of Eating Disorders have highlighted the preponderance and unmet needs of neurodivergent people who experience disordered eating. In this commentary, we encourage researchers to engage with the bigger question of "What's Next?" and consider the type of research that is needed to shift the dial by lowering the incidence and persistence of disordered eating in neurodivergent people. As a starting point, we believe that future research must be guided by the needs and priorities of neurodivergent people with experience of eating disorders. Based on our own experience of community collaboration, we make specific recommendations for future research: (1) Broadening the Scope; such that we expand the focus beyond anorexia nervosa, and consider other manifestations of disordered eating, such as restriction, binge eating and emotional eating, and avoidant restrictive food intake disorder (ARFID), but also acknowledge the impact of other forms of neurodivergence beyond autism (e.g., ADHD), (2) Identifying Causal Mechanisms; moving beyond describing prevalence to studying why and how neurodevelopmental traits are associated with disordered eating (which in turn will inform new intervention design), and (3) Adapting Existing Interventions; understanding how current interventions can be adapted to meet the needs of neurodivergent individuals.
Lead strangulation is a dangerous complication of epicardial pacemaker insertion. This complication has been increasingly highlighted lately. Our institution has recently identified four cases over the past five years. This study’s aim was to 1) identify risk factors for strangulation and 2) prospectively screen existing epicardial pacemaker patients for unrecognized strangulation or features that would prompt closer review. Patients known to the pacemaker clinic with epicardial pacemakers inserted from 2005 to 2023 were included. Electronic health records were used to locate all subjects and gather data. Risk factors were identified using Firth’s penalized method of logistic regression. Forty-five patients were included, of which four (8.8%) had evidence of strangulation. Posterior–anterior (PA) chest radiographs all demonstrated characteristic looping patterns of the pacing leads, with confirmation on CT angiography. All affected patients underwent revision surgery. Implantation at a weight of less than 6.5 kg was associated with a significantly increased incidence of strangulation (OR 25, P 0.044). Other factors including lead length, presence of structural cardiac disease, and dual-chamber insertion were not statistically significant. No patients who were prospectively screened were found to have strangulation. Children undergoing insertion of a pacemaker early in infancy are at particularly high risk of strangulation and should be closely monitored following surgery. Regular chest radiography (every three years) to screen for this complication is advised. Larger multi-center studies to pool data for this relatively rare complication may help identify other risk factors for strangulation.
Background The definition of ‘recovery’ has evolved beyond merely control of problem substance use to include other aspects of health and wellbeing (known as ‘recovery capital’) which are important to prevent relapse to problematic alcohol or other drug (AOD) use. Developing a Recovery Oriented System of Care (ROSC) requires consideration of interventions or services (Recovery Support Services, RSS) designed to build recovery capital which are often delivered alongside established treatment structures. Lived experience and its application to the process of engaging people, changing behaviour and relapse prevention is an essential part of these services. Aim To map out the evidence base for RSS as part of guidance for commissioners of addiction services in each of the 152 local authorities in England. Methods The authors updated the findings of a 2017 systematic review of RSS through a further rapid scoping review, aiming to map out the extent, range and nature of research under six headings: (1) Peer‐based recovery support services (P‐BRSS); (2) Employment support approaches; (3) Recovery housing; (4) Continuing care and recovery check‐ups; (5) Recovery community centres (RCC); and (6) Recovery support services in educational settings. A systematic search of the PubMed, Embase, CINAHL, CENTRAL and PsychINFO databases was conducted. The abstracts of all articles published since 2017 were reviewed by two of the authors, and the full text versions of all relevant articles were obtained and relevant data extracted. A narrative review of the findings was then prepared, mapping them on to the ROSC continuum of care. The review was restricted to adults (over 18 years), but all substances and available outcomes were included. Results Four of the six forms of RSS were well supported by evidence. RCTs of interventions to increase levels of employment demonstrated large effect sizes, and continuing care interventions that extend treatment intervention into the early recovery phase have shown small but significant benefit. Peer‐delivered interventions to link people to ongoing support were associated with decreased rates of relapse and re‐admission, increased engagement, and increased social support for change. However, the variability in the design of these studies means that further work is required to clarify the effective components of the intervention. Studies of recovery housing have also shown positive results, including significant differences from standard care. No controlled studies exist to support RCCs or RSS in educational settings, but the complexity of these interventions and the wide range of potential outcome measures mean that other study designs may be more relevant. Conclusions This monograph provides a structure to help policy makers, commissioners and service providers describe and understand an emerging field of research. Recovery Support Services (RSS) are proving to have clinical, public health and cost utility. A rational social and fiscal response to endemic alcohol or other drug challenges should therefore include the more intensive acute care clinical services linked with more extensive community‐based RSS.
Background The literature is equivocal as to whether the predicted negative mental health impact of the COVID-19 pandemic came to fruition. Some quantitative studies report increased emotional problems and depression; others report improved mental health and well-being. Qualitative explorations reveal heterogeneity, with themes ranging from feelings of loss to growth and development. Objective This study aims to analyze free-text responses from children and young people participating in the Children and Young People With Long COVID study to get a clearer understanding of how young people were feeling during the pandemic. Methods A total of 8224 free-text responses from children and young people were analyzed using InfraNodus, an artificial intelligence–powered text network analysis tool, to determine the most prevalent topics. A random subsample of 411 (5%) of the 8224 responses underwent a manual sentiment analysis; this was reweighted to represent the general population of children and young people in England. Results Experiences fell into 6 main overlapping topical clusters: school, examination stress, mental health, emotional impact of the pandemic, social and family support, and physical health (including COVID-19 symptoms). Sentiment analysis showed that statements were largely negative (314/411, 76.4%), with a small proportion being positive (57/411, 13.9%). Those reporting negative sentiment were mostly female (227/314, 72.3%), while those reporting positive sentiment were mostly older (170/314, 54.1%). There were significant observed associations between sentiment and COVID-19 status as well as sex (P=.001 and P<.001, respectively) such that the majority of the responses, regardless of COVID-19 status or sex, were negative; for example, 84.1% (227/270) of the responses from female individuals and 61.7% (87/141) of those from male individuals were negative. There were no observed associations between sentiment and all other examined demographics. The results were broadly similar when reweighted to the general population of children and young people in England: 78.52% (negative), 13.23% (positive), and 8.24% (neutral). Conclusions We used InfraNodus to analyze free-text responses from a large sample of children and young people. The majority of responses (314/411, 76.4%) were negative, and many of the children and young people reported experiencing distress across a range of domains related to school, social situations, and mental health. Our findings add to the literature, highlighting the importance of specific considerations for children and young people when responding to national emergencies.
Background Enteral tube feeding is used for children who are unable to meet their nutritional requirements orally. Gastrointestinal symptoms are some complications that can occur in enteral tube‐fed patients. Blended tube feeds (BTFs) for children who are gastrotomy tube‐fed have significantly increased in the last decade. BTF refers to homemade food that has been liquidised for enteral tube feeds. An increasing amount of evidence suggests that children on BTF have improved feed tolerance. It is unknown whether children admitted to a hospital established on a BTF can continue a BTF due to the potential barriers such as catering processes, staffing hours (limited to syringe bolus feeding) and food safety concerns. This national cross‐sectional survey aimed to explore the use of BTF in a paediatric hospital setting. Methods This was a prospective, cross‐sectional, practice‐based survey of registered paediatric dietitians who work in an inpatient care setting to explore the use of BTF. The final survey consisted of 13 questions and took dietitians approximately 15 min to complete. The questions focused on the dietitian's experience, knowledge and confidence in children on a BTF. Results Across the United Kingdom, 51 hospitals completed the survey. Of these, 16 of 19 were specialist children's hospitals (79% response rate) and 35 of 89 were general paediatric hospitals (39% response rate). All responders were paediatric dietitians. 49 of 51 (96%) dietitians knew of the British Dietetic Association (BDA) Practice Toolkit for Blended diets. Dietitians were asked to estimate on average per month how many children were admitted on a BTF; 41% (21 of 51) of dietitians reported that on average there are one to five children admitted on a BTF. There was no significant difference in the number of children admitted on a BTF between a specialist and a general children's hospital ( χ ² statistic = 4.96, p value < 0.08). The number of dietitians who had clinical guidelines to support children admitted on a BTF was 49% (25 of 51). Specialist children's hospitals were more likely to have a clinical guideline compared with a general hospital (χ ² statistic = 6.348, p value = 0.01). However, only 18 of 51 (35%) dietitians reported being confident or very confident to review a child on a BTF. The most common perceived benefit was that parents/carers could incorporate family foods into their child's diet. 26% reported that a varied diet was beneficial in relation to the gut microbiome. If a BTF was contraindicated for children admitted to a hospital (immunocompromised, post‐pyloric feeding or intensive care), 49 of 51 (96%) dietitians reported they would use an enteral formula with food‐derived ingredients (Compleat paediatric—Nestle Health Science) as an alternative to a BTF. Conclusion BTF continues to grow in popularity. Our survey reported that children on BTF are frequently admitted to the hospital. There is growing evidence to support BTF in relation to family psychosocial health and feed tolerance. Dietitians must keep abreast of this fast‐evolving area practice to ensure that they are the experts in BTF. When a BTF is contraindicated, an enteral formula with food‐derived ingredients is a suitable alternative. Issues such as microbial contamination, nutritional composition, and adequacy of diluted BTF need further exploration.
Background Motion correction methods based on slice-to-volume registration (SVR) for fetal magnetic resonance imaging (MRI) allow reconstruction of three-dimensional (3-D) isotropic images of the fetal brain and body. However, all existing SVR methods are confined to research settings, which limits clinical integration. Furthermore, there have been no reported SVR solutions for low-field 0.55-T MRI. Objective Integration of automated SVR motion correction methods directly into fetal MRI scanning process via the Gadgetron framework to enable automated T2-weighted (T2W) 3-D fetal brain and body reconstruction in the low-field 0.55-T MRI scanner within the duration of the scan. Materials and methods A deep learning fully automated pipeline was developed for T2W 3-D rigid and deformable (D/SVR) reconstruction of the fetal brain and body of 0.55-T T2W datasets. Next, it was integrated into 0.55-T low-field MRI scanner environment via a Gadgetron workflow that enables launching of the reconstruction process directly during scanning in real-time. Results During prospective testing on 12 cases (22–40 weeks gestational age), the fetal brain and body reconstructions were available on average 6:42 ± 3:13 min after the acquisition of the final stack and could be assessed and archived on the scanner console during the ongoing fetal MRI scan. The output image data quality was rated as good to acceptable for interpretation. The retrospective testing of the pipeline on 83 0.55-T datasets demonstrated stable reconstruction quality for low-field MRI. Conclusion The proposed pipeline allows scanner-based prospective T2W 3-D motion correction for low-field 0.55-T fetal MRI via direct online integration into the scanner environment. Graphical Abstract
Purpose Recent efforts have sought to streamline gastrostomy insertion care, particularly length of stay (LOS). We report our initial experience with day-case gastrostomy (DCG) insertion. Method Retrospective review (April 2018–2024) of all primary gastrostomy insertions. Patients discharged the same day as the procedure were defined as DCG. Demographic, operative, and clinical data were recorded. All cases were treated according to a standardized feeding pathway. Results Of 432 gastrostomies formed, 15 were DCG; median age 3.5 (0.7–16.9) years, LOS 12 h (9–15 h). The most common indication was nutritional supplementation (n = 9). Gastrostomy technique was single-stage percutaneous rapid insertion of gastrostomy button (SPRING n = 5) or percutaneous endoscopic gastrostomy (PEG n = 10). Prior to insertion, 6/15 DCG were established on nasogastric (NG) feeding, 8 did not use NG feeding, and 1 had occasional NG feeds. The majority (13/15) were performed on morning operating lists. There were 4 minor complications; 2 required readmission. Conclusion DCG in selected cases is feasible and safe. Most cases were performed on morning operating list, but fewer than half had prior experience of nasogastric tube feeding. We suggest additional pathway modifications to improve DCG uptake.
Background Nearly 3% of adults have attention-deficit and hyperactivity disorder (ADHD), although in the UK, most are undiagnosed. Adults with ADHD on average experience poorer educational and employment outcomes, worse physical and mental health and are more likely to die prematurely. No studies have yet used mortality data to examine the life expectancy deficit experienced by adults with diagnosed ADHD in the UK or worldwide. Aims This study used the life-table method to calculate the life-expectancy deficit for people with diagnosed ADHD using data from UK primary care. Method A matched cohort study using prospectively collected primary care data (792 general practices, 9 561 450 people contributing eligible person-time from 2000–2019). We identified 30 039 people aged 18+ with diagnosed ADHD, plus a comparison group of 300 390 participants matched (1:10) by age, sex and primary care practice. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy for people aged 18+ with diagnosed ADHD. Results Around 0.32% of adults in the cohort had an ADHD diagnosis, ~1 in 9 of all adults with ADHD. Diagnoses of common physical and mental health conditions were more common in adults with diagnosed ADHD than the comparison group. The apparent reduction in life expectancy for adults with diagnosed ADHD relative to the general population was 6.78 years (95% CI: 4.50 to 9.11) for males, and 8.64 years (95% CI: 6.55 to 10.91) for females. Conclusions Adults with diagnosed ADHD are living shorter lives than they should. We believe that this is likely caused by modifiable risk factors and unmet support and treatment needs in terms of both ADHD and co-occurring mental and physical health conditions. This study included data from adults with diagnosed ADHD; the results may not generalise to the entire population of adults with ADHD, the vast majority of whom are undiagnosed.
The application of international recommendations for paediatric maintenance haemodialysis (HD) could be strengthened by national laws or written recommendations. Our aim was therefore to describe the national rules governing paediatric maintenance HD in European countries. A national representative, approved by the president of each paediatric nephrology society, was contacted in all 42 European countries to complete two online questionnaires. Answers were received from 36 countries. The population served by HD centres varies from 83,000 to 1,197,000 residents below 18 years of age and the estimated mean number of children on HD per centre from 0.2 to 13.5. The lowest age at which a child can be dialysed in an adult centre varies from 0 to 18 years. Laws or written national recommendations specifying: this age, the need for a paediatrician as part of medical team in mixed adult–paediatric centres, the minimum number of doctors per centre and the number of patients per nurse or nurse’s aide required during sessions exist in only 25, 22, 22, 44 and 8% of the countries, respectively. Similarly, dietitians, social workers, school service, psychologists and play specialists/youth workers are required by law or written national recommendations in 36, 28, 36, 31 and 14% of countries, respectively. Laws or written national recommendations for paediatric maintenance HD are rare in European countries and very heterogeneous when they exist. This calls for discussion among paediatric and adult nephrologists and health authorities on the organisation of safe and effective paediatric HD practices. A higher resolution version of the Graphical abstract is available as Supplementary information
Introduction Crohn’s disease (CD) is a chronic, immune-mediated inflammatory bowel disease (IBD), presenting with symptoms of abdominal pain and bleeding from the gastrointestinal tract. There is no known cure. In vitro-expanded ‘thymus-derived’ regulatory T cells (tTreg) have shown promise in preclinical models of IBD, leading to interest in their use as a potential therapy in CD. We present a study protocol for a first-in-human study of Tregs for IBD using ex vivo Treg expansion. This study will explore the preliminary safety and tolerability of a single dose of Treg immunotherapy and will inform the design of a subsequent larger trial. Methods and analysis Four patients will be recruited from gastroenterology clinics at Guy’s and St Thomas’ NHS Foundation Trust. Eligible participants are those who are at least 18 years old, have a diagnosis of active moderate to severe CD and have failed to respond to or tolerate at least two prior lines of standard medication. Participants receive a single dose of autologous ex vivo-expanded Tregs and will be followed up to week 21 to collect safety and exploratory efficacy data. Additional safety monitoring will occur at 1 and 2 years post-dose. The primary endpoint is defined as the occurrence of dose-limiting toxicity occurring within 5 weeks post-infusion. Ethics and dissemination The study protocol and related documents have been approved by a NHS Research Ethics Committee, the Health Research Authority and the Medicines and Healthcare products Regulatory Agency for Clinical Trial Authorisation. It is intended that the results of the trial will be presented at international conferences and will be submitted for publication in a peer-reviewed scientific journal. Trial registration number NCT03185000
Recent clinical trials on slowing dementia progression have led to renewed focus on finding safer, more effective treatments. One approach to identify plausible candidates is to assess whether existing medications for other conditions may affect dementia risk. We conducted a systematic review to identify studies adopting a data‐driven approach to investigate the association between a wide range of prescribed medications and dementia risk. We included 14 studies using administrative or medical records data for more than 130 million individuals and 1 million dementia cases. Despite inconsistencies in identifying specific drugs that may modify Alzheimer's or dementia risk, some themes emerged for drug classes with biological plausibility. Antimicrobials, vaccinations, and anti‐inflammatories were associated with reduced risk, while diabetes drugs, vitamins and supplements, and antipsychotics were associated with increased risk. We found conflicting evidence for antihypertensives and antidepressants. Drug repurposing for use in dementia is an urgent priority. Our findings offer a basis for prioritizing candidates and exploring underlying mechanisms. Highlights ·We present a systematic review of studies reporting association between drugs prescribed for other conditions and risk of dementia including 139 million people and 1 million cases of dementia. ·Our work supports some previously reported associations, for example, showing decreased risk of dementia with drugs to treat inflammatory disease and increased risk with antipsychotic treatment. ·Antimicrobial treatment was perhaps more surprisingly associated with decreased risk, supportive of recent increased interest in this potential therapeutic avenue. ·Our work should help prioritize drugs for entry into adaptive platform trials in Alzheimer's disease and will serve as a useful resource for those investigating drugs or classes of drugs and risk of dementia.
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54 members
Alison Tingle
  • Science Research & Evidence
Fayyaz Ahmed
  • Department of Health
Carole Fry
  • Communicable Diseases
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